[Malignant hypertension in a young man with renal artery occlusion diagnosed with magnetic resonance angiography]. / Maligne hypertensie bij een jongeman met nierarterieafsluiting gediagnosticeerd met magnetische-resonantieangiografie.

A male aged 22 years developed a hypertensive crisis with encephalopathy after his antihypertensive medication had been discontinued with a view to extended diagnostics. Immediate intensive treatment led to rapid and complete recovery. By using gadopentetate acid enhanced magnetic resonance angiography it is possible to obtain a clear image of the morphology of the kidneys and the renal vasculature without the use of iodinated contrast media and arterial catheterisation. This technique revealed an occluded renal artery and a recent infarction that possibly had led to the serious and threatening events.

Dynamic distribution and dosimetric evaluation of human non-specific immunoglobulin G labelled with 111In or 99Tcm.

This study presents data on the dynamic distribution and dosimetry of 111In- and 99Tcm-labelled human non-specific immunoglobulin G (IgG), two recently developed radiopharmaceuticals for the detection of infection and inflammation. Five healthy volunteers were injected with 20-75 MBq 111In-IgG and seven patients were injected with 740 MBq 99Tcm-hydrazinonicotinamide derivative (HYNIC)-IgG. Blood samples, urine and feces were collected. Whole-body gamma camera imaging studies were performed. The activity in source organs was quantified using the conjugate view counting method and a partial background subtraction technique. Dosimetric calculations were performed using the MIRD technique. For 111In-IgG, the mean biological half-times in the blood were 0.90 and 46 h for the a- and b-phase, respectively. For 99Tcm-HYNIC-IgG, these half times were 0.46 and 45 h. For 111In-IgG, the mean cumulative urinary excretion in the first 48 h was 18% of the injected dose, while excretion in the feces was less than 2% of the injected dose. For 99Tcm-HYNIC-IgG, the whole-body retention was always 100% up to 24 h. The mean absorbed doses in the liver, spleen, kidneys, red marrow and testes from 111In-IgG were 0.8, 0.7, 1.2, 0.3 and 0.4 mGy MBq-1 respectively. The mean absorbed doses for 99Tcm-HYNIC-IgG to these organs were 16, 24, 15, 10 and 22 mu Gy MBq-1 respectively. The mean effective dose was 0.25 mSv MBq-1 and 8.4 mu Sv MBq-1 for 111In-IgG and 99Tcm-HYNIC-IgG respectively. In conclusion, the radiation absorbed doses for both 111In-IgG and 99Tcm-HYNIC-IgG are low and, therefore, these radiopharmaceuticals can be administered safely from a radiation risk perspective.

Technetium-99m labeled to human immunoglobulin G through the nicotinyl hydrazine derivative: a clinical study.

UNLABELLED: A novel method to label polyclonal human immunoglobulin G (IgG) with 99mTc through the nicotinyl hydrazine derivative (HYNIC) has shown promising results in the detection of experimental infection. In this study, 99mTc-labeled HYNIC-IgG was directly compared to (111)In-labeled diethylenetriaminepentaacetic acid (DTPA)-IgG in patients suspected of infectious or inflammatory disease. METHODS: Thirty-seven patients (22 women and 15 men; mean age = 54 yr, range = 17-78 yr) with 39 suspected infectious or inflammatory foci were prospectively studied. After administration of 740 MBq 99mTc-HYNIC-IgG, imaging was performed at 4 and 24 hr postinjection. To avoid cross-over activity, (111)In-DTPA-IgG was injected 24 hr after 99mTc-HYNIC-IgG and imaged at 4, 24 and 48 hr postinjection. The scintigraphic results were confirmed by microbiological, histological, radiological and clinical methods. RESULTS: Technetium-99m-HYNIC-IgG and (111)In-DTPA-IgG scintigraphy showed 100% concordancy. All 17 patients with proven infection or inflammation (19 foci, mainly localized in the locomotor system) had positive scintigraphic findings. No false-negative scintigrams were recorded. In three patients, the scintigrams were concordantly false-positive. As a result, the sensitivity and specificity of imaging infectious or inflammatory foci with 99mTc-HYNIC-IgG and (111)In-DTPA-IgG in these patients were 100% and 85%, respectively. CONCLUSION: Technetium-99m-HYNIC-IgG scintigraphy is equally as effective as (111)In-IgG scintigraphy for the detection of infection and inflammation. The apparent physical and logistic advantages of 99mTc over (111)In make 99mTc-HYNIC-IgG a promising new radiopharmaceutical for imaging infection and inflammation.

Evaluation of infections of the locomotor system with indium-111-labeled human IgG scintigraphy.

UNLABELLED: Indium-111-labeled human nonspecific immunoglobin G (111In-IgG) is one of the newer agents suggested for scintigraphic evaluation of infection and inflammation. In this study, the utility of this agent was studied in routine clinical practice. METHODS: A dose of 75 MBq 111In labeled to 2 mg IgG (MacroScint) was administered intravenously in 226 patients with 232 possible foci of infection or inflammation. Imaging was performed 4, 24 and 48 hr postinjection. The results were verified by culture, obtained either surgically (42%) or via puncture (19%) and long-term clinical and roentgenological follow-up (39%). Follow-up data were used in patients of whom the vast majority had a negative work-up, including negative 111In-IgG scintigraphy. RESULTS: All infected total hip (THA) and total knee arthroplasties, focal osteomyelitis, diabetic foot infections, septic arthritis and soft-tissue infections were detected (61 foci). Only one patient with early, low-grade spondylodiscitis was false negative with 111In-IgG. Since 111In-IgG scintigraphy does not discriminate between infectious and sterile inflammation, careful interpretation is necessary in cementless THA up to 1 yr after insertion, uptake only around the neck of the femoral component of a THA, recent fractures and pseudarthrosis, in which uptake may be caused by sterile inflammation and not by infection (specificity for inflammation 100%, specificity for infection of 77%). CONCLUSION: Indium-111-IgG scintigraphy is a very sensitive tool for detection of infectious bone and joint disease. Moreover, when uptake patterns of 111In-IgG, which are characteristic for sterile inflammation, are excluded, infection can be ruled out with a high degree of certainty.

Hip and knee arthroplasty infection. In-111-IgG scintigraphy in 102 cases.

We studied indium-111-labeled immunoglobulin G (In-111-IgG) scintigraphy for evaluation of total hip and knee arthroplasty infection in 100 patients (102 arthroplasties) where infection was suspected (85 total hip and 17 total knee replacements, 23 of which proved to be infected, all but 2 late infections). The sensitivity of In-111-IgG scintigraphy for infection was 1.0, for hip and knee arthroplasties the specificities were 0.8 and 0.5, respectively. False-positive results for infection occurred in cementless total hip arthroplasties up to 14 months after implantation. Aseptic inflammation due to formation of ectopic ossification and foreign-body response, following wear of the polyethylene socket, was responsible for false-positive results. The images should be read in conjunction with radiographs, which reduces the rate of false-positive results. In-111-IgG is a highly sensitive and fairly specific tool for detecting of late infection of total hip and total knee arthroplasties.

Different behaviour of radioiodinated human recombinant interleukin-1 and its receptor antagonist in an animal model of infection.

Recently, we demonstrated that radiolabelled interleukin-1alpha (IL-1) specifically accumulates in focal infection in mice through interaction with its receptor. Unfortunately, systemic side-effects of IL-1 limit its clinical application. We investigated whether this problem could be circumvented by using the interleukin-1 receptor antagonist (IL-1ra), an equally sized protein that binds to the same receptors as IL-1 without induction of biological effects. Biodistribution of 125I-IL-1 and 125I-IL-1ra was determined in Swiss mice with Staphylococcus aureus-induced abscesses in the left calf muscle at 4, 12, 24 and 48 h after injection of either 0.4 MBq 125I-IL-1 or 0.4 MBq 125I-IL-1ra. In vitro, the proteins displayed similar binding characteristics. High-performance liquid chromatographic analysis revealed a tendency for IL-1ra to associate with serum proteins. Both proteins rapidly cleared from most organs. However, the abscess uptake of 125I-IL-1ra was significantly lower than that of 125I-IL-1 at all time points (48 h p.i.: 0.06+/-0. 01%ID/g vs 0.60+/-0.04%ID/g; P<0.02). The abscess-to-contralateral muscle ratios did not exceed 15.5+/-2.9 for 125I-IL-1ra, while the ratios for 125I-IL-1 reached 46.9+/-5.7 at 48 h p.i. Despite similar in vitro receptor binding, the abscess uptake of IL-1ra was much lower than that of IL-1. The interaction of IL-1ra with serum proteins in vivo may reduce its availability for receptor binding in the infection. Although on theoretical grounds IL-1ra is very interesting, these characteristics will prevent its development as a clinically useful radiopharmaceutical to image infection.

Retention of technetium-99m in infectious foci in rats after release from technetium-99m labelled human non-specific polyclonal immunoglobulin G: a dual-label study with hydrazinonicotinamido and iminothiolano immunoglobulin.

In an effort to contribute to the understanding of the mechanism of uptake of technetium-99m labelled non-specific polyclonal human immunoglobulin G (hIgG) in inflammatory lesions we compared the tissue distribution of double-labelled 99mTc-hydrazinonicotinamido (HYNIC) hIgG-14C and 99mTc-iminothiolano hIgG-14C in groups of five Wistar rats with a Staphylococcus aureus infection of the left calf muscle between 2 h p.i. and 24 h p.i. The stability of the two double-labelled hIgG preparations was evaluated in vitro and in plasma in vivo by high-performance liquid chromatography (HPLC) analysis. At 24 h after injection of 99mTc-HYNIC-hIgG-14C the abscess uptake of 99mTc (1.5% ID/g+/-0.2% ID/g) was significantly higher (P<0.01) than the 14C uptake (1.0% ID/g+/-0.1% ID/g). After injection of 99mTc-iminothiolano hIgG-14C no significant difference (P=0.08) was found between the abscess uptake of the two radionuclides at 24 h p.i. (99mTc: 0.8% ID/g+/-0.1% ID/g; 14C: 0.90% ID/g+/-0.09% ID/g). HPLC analysis of plasma samples revealed release of 99mTc from both double-labelled immunoglobulin preparations. This phenomenon was more pronounced for iminothiolano hIgG than for HYNIC hIgG (43% vs 18%). In most tissues other than abscesses significant differences were also found between the 99mTc and the corresponding 14C uptake. Our results demonstrate that the chemical form in which 99mTc is bound to hIgG severely influences its release from hIgG and its retention in infections.

Detecting infection and inflammation with technetium-99m-labeled Stealth liposomes.

UNLABELLED: The performance of 99mTc Stealth liposomes was investigated in various rat models. METHODS: Preformed polyethyleneglycol-containing liposomes with encapsulated reduced glutathione, were radiolabeled using the lipophilic 99mTc-HMPAO. The labeled liposomes were intravenously administered to rats with focal S. aureus or E. coli infection, or turpentine-induced inflammation. For comparison, Tc-99m-nanocolloid- and 99mTc-labeled nonspecific IgG were tested. In rats with Pneumocystis carinii pneumonia (PCP), Tc-99m-liposomes were directly compared to In-111 labeled nonspecific IgG. RESULTS: Technetium-99m-liposomes accumulated in the infectious and inflammatory muscle foci over 24 hr (0.59% injected dose per gram tissue (%ID/g) for S. aureus; 1.18 %ID/g for turpentine). Abscess-to-muscle ratios increased to values as high as 24.0, 41.7 and 44.5 for the respective models at 24 hr postinjection. Technetium-99m-liposomes visualized the foci as early as 1 hr postinjection. Technetium-99m-IgG visualized S. aureus infection, but abscess-to-muscle ratios and abscess uptake at the later time points were significantly lower. Technetium-99m-nanocolloid failed to visualize any of the muscle foci. In PCP however, 99mTc-liposomes did not show preferential localization in the infection. The control agent 111In-IgG showed a significant, two-fold increase in lung uptake. CONCLUSION: Technetium-99m-Stealth liposomes preferentially accumulated in abscesses, leading to very high target-to-nontarget ratios. This property appears to be related to a process based on uptake of long-circulating particles. In a specific type of infection, i.c. PCP, 99mTc-liposomes did not accumulate in diseased lung tissue, thus mimicking the in vivo behavior of labeled leukocytes.

Biodistribution of 111In-labelled IgG and IgM in experimental infection.

Both the protein used and the conjugation method are factors which may be relevant for targeting infection with 111In-labelled proteins. In this study, human immunoglobulin G (IgG), conjugated to either DTPA or LiLo, and LiLo conjugated human immunoglobulin M (IgM) were evaluated. In rats with Staphylococcus aureus calf muscle infection, biodistribution was determined 6, 24 and 48 h after the injection of 111In-DTPA-IgG, 111InLiLo-IgG or 111In-LiLo-IgM. Absolute abscess uptake of 111In-LiLo-IgG was significantly higher than that of 111In-DTPA-IgG (P < 0.05). Since blood clearance of 111In-LiLo-IgG was initially significantly slower (P < 0.01), the higher abscess uptake did not result in higher abscess-to-background ratios. 111In-LiLo-IgG accumulated to a greater extent in the liver (P < 0.001). 111In-DTPA-IgG showed higher uptake in the kidneys and bone marrow (P < 0.001 and P < 0.01, respectively). Although decreasing over time, 111In-LiLo-IgM showed reasonable abscess uptake and rapid blood clearance, resulting in higher abscess-to-background ratios compared with 111In-LiLo-IgG (P < 0.01). However, liver and spleen uptake were three- to four-fold higher than that of 111In-LiLo-IgG (P < 0.001). Compared with DTPA-conjugation, chelation with LiLo has a minor influence on abscess targeting of 111In-labelled IgG. However, differences in blood clearance and organ uptake do occur. 111In-LiLo-IgM shows high relative accumulation in abscesses as well as high liver and spleen uptake. 111In-LiLo-IgM appears promising for imaging infection outside the trunk region.

Pharmacokinetics, biodistribution and biological effects of intravenously administered bispecific monoclonal antibody OC/TR F(ab')2 in ovarian carcinoma patients.

The bispecific monoclonal antibody (biMAb) OC/TR combines the anti-ovarian-cancer reactivity of the MOv18 monoclonal antibody (MAb) with the reactivity of an anti-CD3 MAb. Pre-clinical studies have indicated that this biMAb is able to redirect the cytolytic activity of T cells towards tumour cells, resulting in efficient tumour-cell lysis. To assess the clinical potential of systemic biMAb-based cancer therapy we initiated a study in ovarian-cancer patients. Five patients suspected of ovarian cancer received 123I-OC/TR F(ab')2 i.v. Unexpectedly, the first patient developed side effects (grade III-IV toxicity) starting 30 min after infusion (p.i.) of 1 mg of OC/TR F(ab')2. After approval of the Ethical Committee, the study was continued at lower dose levels (0.1 mg; 0.2 mg). However, at the 0.2-mg dose level similar side effects were observed. FACS analysis indicated that all peripheral T cells were coated with biMAb immediately following the infusion. The cytokines tumour necrosis factor-alpha, interferon-gamma and interleukin-2 showed maximum serum concentrations 2 h p.i. Tumour uptake ranged from 0.8 to 1.9% ID/kg, resulting in tumour/background ratios of 3 to 8. Our results suggest that at higher antibody dose levels OC/TR F(ab')2 causes T-cell activation with acute release of cytokines. Only low doses of biMAb can be administered safely. Despite the interaction with T cells, OC/TR F(ab')2 preferentially localizes in tumours following i.v. administration, thus offering therapeutic perspectives.

Technetium-99m labelled hydrazinonicotinamido human non-specific polyclonal immunoglobulin G for detection of infectious foci: a comparison with two other technetium-labelled immunoglobulin preparations.

Recently a new linker - hydrazinonicotinate (HYNIC) - was introduced for labelling of proteins and peptides with technetium-99m. HYNIC and other linkers have been used for labelling of human non-specific polyclonal immunoglobulin G (hIgG) with 99mTc for the detection of infections. In this study we compared the tissue distribution of three different 99mTc-hIgG preparations in groups of five Wistar rats with a focal intramuscular infection with Staphylococcus aureus. We compared 99mTc-HYNIC-hIgG with 99mTc-hIgG labelled via the so-called Schwarz method (reduction of disulphide bonds) and with the 99mTc-labelled commercially available Technescan-HIG. Unlike the HYNIC linker, in the two other labelling methods free sulph-hydryl groups are involved in the binding of 99mTc. High-performance liquid chromatography analysis of the labelled preparations and of plasma samples revealed aggregate or polymer formation in all three agents; this was least pronounced in the product labelled by means of the Schwarz method. The tested preparations did not show signs of degradation in vitro. The difference in linker chemistry was reflected in the tissue distribution. Thus the biodistribution of 99mTc-HYNIC-hIgG was significantly different from the distribution of the two other preparations: abscess (1.4%+/-0.2%ID/g), muscle, liver, spleen, plasma, lung, bone marrow, and small intestine concentrations were higher at 24 h p.i.; kidney uptake (1.19%+/-0.08%ID/g) was significantly lower. The abscess-to-plasma and the abscess-to-muscle ratios (0.5 and 11, respectively), however, were in the same range for the three preparations tested. Quantitative analysis of the scintigraphs revealed that the total body clearance of 99mTc-HYNIC-hIgG was significantly slower than for the other agents. The abscess uptake of 99mTc-HYNIC-hIgG as a percentage of the remaining body activity was significantly higher. Based on its high abscess uptake, its low uptake in the kidneys and the high percentage of its abscess uptake in relation to the remaining body activity, we conclude that 99mTc-HYNIC-hIgG seems superior to the two other preparations tested for the detection of infections.

The uptake mechanisms of inflammation- and infection-localizing agents.

Over the past 30 years, a wide variety of radiopharmaceuticals have been proposed for the scintigraphic detection of inflammatory and infectious disease. All radiopharmaceuticals yield a functional image of a process placed somewhere in the cascade of reactions in inflammation, this being the common pathway of response to tissue injury. This paper discusses relevant aspects of the biodistribution, in vivo kinetics and mechanisms of uptake of both clinically used and experimental radiopharmaceuticals that have been proposed for the scintigraphic detection of focal inflammation and infection.

Nuclear arthrography: combined scintigraphic and radiographic procedure for diagnosis of total hip prosthesis loosening.

UNLABELLED: Radiographic arthrography and bone scintigraphy are common diagnostic procedures used for evaluating total hip prostheses. In this study, both techniques are combined, and nuclear contrast imaging (nuclear arthrography) is added. The efficacy of the procedures is evaluated. METHODS: After intravenous injection of 99mTc-methylene diphosphonate (MDP), standard radiographic arthrography was performed in 105 patients (107 prostheses). The radiographic contrast medium was mixed with insoluble 111In-colloid (5 MBq/20 ml). After completion of the radiographic arthrography, nuclear arthrography was performed, and multiple-view dualisotope images (111In, 247-keV peak only) were recorded. Images were interpreted by superposition of the 111In image and the corresponding 99mTc-MDP image, the latter serving as a landmark for the position of the prosthesis and osseous structures. Findings at surgery were used as the gold standard. RESULTS: In both cemented and uncemented acetabular and femoral components, nuclear arthrography performed better than or equal to radiographic arthrography (70%-90% and 60%-75%, respectively). Nuclear arthrography had higher diagnostic accuracy than 99mTc-MDP images alone. CONCLUSION: Nuclear arthrography is a sensitive technique for detection of loosening of prostheses, offering added value over radiographic arthrography and bone scanning alone, especially for evaluation of the femoral component. Radiographic arthrography remains necessary not only for adequate deposition of contrast agents but also for detailed evaluation of osseous structures.

Specific targeting of infectious foci with radioiodinated human recombinant interleukin-1 in an experimental model.

In the present study, radioiodinated human recombinant interleukin-1 (IL-1) was investigated for its potential to image infectious foci in vivo in an animal model of infection. Twenty-four hours after induction of a Staphylococcus aureus abscess in the left calf muscle, mice were i.v. injected with both iodine-125 labelled IL-1 and iodine-131 labelled myoglobin, a size-matched control agent. The animals were killed for tissue biodistribution studies at 2, 6, 12, 24 and 48 h p.i. Gamma camera images were obtained at 6, 24 and 48 h after injecting mice with 123I-IL-1. Radioiodinated IL-1 rapidly cleared from the body; after 12 h the abscess was the organ with the highest activity. The absolute abscess uptake of 125I-IL-1 remained high compared to 131I-myoglobin, resulting in significantly higher abscess-to-muscle ratios of 125I-IL-1 compared to 131I-myoglobin. The ratios of 125I-IL-1 reached the ultimate value of 44.4+/-10.8 at 48 h p.i., whereas the ratios of 131I-myoglobin did not exceed 5.9+/-0.7. Gamma camera imaging revealed clearly visible abscesses. In conclusion, our results demonstrate specific retention of radioiodinated IL-1 in the abscess, presumably by interaction of IL-1 with its receptor on the inflammatory cells. The high target-to-background ratios that were obtained over the course of time indicate that the IL-1 receptor may be a valuable target for the imaging of infectious foci.

Utility of scintigraphic methods in patients with fever of unknown origin.

BACKGROUND: We assessed the utility of scintigraphy with indium 111-labeled polyclonal human IgG scintigraphy in patients with fever of unknown origin that fulfilled the criteria of temperature of 38.3 degrees C or more for at least 3 weeks and no diagnosis during 1 week of hospital admission. We compared the utility of this technique with results of scintigraphic techniques reported in the literature. METHODS: Data for all patients seen at our university hospital in whom 111In-IgG scanning was performed were analyzed and checked for the criteria for fever of unknown origin. The literature on the utility of scintigraphic techniques in patients with fever of unknown origin was reviewed. RESULTS: We studied 24 patients with fever of unknown origin. In 13 patients, focal 111In-IgG accumulation was observed. In nine (38%) of those, the positive 111In-IgG scintigram led to the final diagnosis; in the other four patients (17%), the scintigraphic findings were not helpful. In the 11 patients with negative 111In-IgG scans, extensive diagnostic workup produced no infection as the final diagnosis in nine patients (38%), one had an abscess in a renal cyst that was detected several months later, and in the other the cause of fever was an infected intravenous line. The overall sensitivity and specificity of 111In-IgG scintigraphy were 81% and 69%, respectively. The positive predictive value was 69% and the negative predictive value was 82%. CONCLUSIONS: Our results show that 111In-IgG scintigraphy significantly contributed to the diagnostic process in patients with fever of unknown origin. A positive scan increased the likelihood of finding the cause of the fever, and a negative scan ruled out an inflammatory component with a high degree of certainty. These data compare favorably with data in the literature concerning other radiopharmaceuticals; a larger prospective evaluation of this technique is indicated.

Tumour targeting of the anti-ovarian carcinoma x anti-CD3/TCR bispesific monoclonal antibody OC/TR and its parental MOv18 antibody in experimental ovarian cancer.

The anti-tumour x anti-T-cell bispecific monoclonal antibody (biMAb) OC/TR is a biologically produced biMAb combining the anti-ovarian carcinoma activity of the MOv18 MAb with anti-CD3/T-cell receptor (TCR) complex activity. In this study, the in vitro binding characteristics of the OC/TR biMAb and its tumour targeting potential in nude mice with Hela tumours was studied. Scatchard analysis revealed that the affinity constant of the biMAb was 7 times lower than the affinity of the parental MOv18 antibody. Uptake of the OC/TR antibody in the Hela xenografts in nude mice was significantly higher than the tumour uptake of an irrelevant control antibody, indicating that the radioiodinated OC/TR biMAb specifically localized in the tumour xenografts. However, tumour uptake was significantly lower than the tumour uptake of the parental MOv18 antibody. This reduced tumour uptake most likely is a result of its reduced affinity. We conclude that, despite the loss of bivalent tumour cell binding, the biMAb OC/TR can still specifically localize in tumours. This indicates that the first prerequisite of an effective therapeutic approach using systemically applied biMAb can be met. Whether the interaction with human T-cells will affect the tumour targeting potential of the biMAb in patients remains to be investigated.

Sterically stabilized liposomes labeled with indium-111 to image focal infection.

UNLABELLED: To determine the potential of sterically stabilized liposomes to image infectious and inflammatory foci, the in vivo behavior of 111In-labeled PEGylated (coated with polyethylene glycol) liposomes was studied in a rat model. METHODS: Indium-111-PEGylated lipsomes were administered intravenously to rats infected with S. aureus in the left calf muscle. The distribution of the radiolabel was studied by gamma counting of dissected tissues and gamma camera imaging for 48 hr. As a reference agent, the preparation of 111In-IgG was included in these studies. RESULTS: Clearance of the PEGylated liposomes from the blood compartment was similar to the clearance of 111In-IgG in this model (t1/2 approximately 20 hr). Uptake of the radiolabel in the abscess with the 111In-liposomes was twice as high as the uptake following injection of 111In-IgG (2.7%ID/g versus 1.1%ID/g at 48 hr postinjection). Tissue counting revealed that abscess-to-muscle ratios reached values up to 20 and 34 (24 and 48 p.i., respectively). As early as 1 hr postinjection, the abscess could be visualized scintigraphically. CONCLUSION: The in vivo characteristics of this liposomal formulation in this rat model indicate that sterically stabilized liposomes labeled with gamma emitters might be a valuable addition to the arsenal of radiopharmaceuticals currently used for infection imaging.

Dissociation of indium from indium-111-labelled diethylene triamine penta-acetic acid conjugated non-specific polyclonal human immunoglobulin G in inflammatory foci.

Several investigators have reported retention of indium-111 in infectious foci after intravenous injection of 111In-labelled immunoglobulin G (IgG). With this study we intended to test the hypothesis that, upon administration of 111In-diethylene triamine penta-acetic acid (DTPA-IgG), 111In is retained in the infectious foci after dissociation from IgG. Therefore we measured the tissue distribution of double-labelled 111In-DTPA-IgG-(carbon-14) in rats with a focal infection and compared the results with corresponding data for DTPA-IgG-(14C). DTPA-conjugated IgG was labelled with 111In via citrate transchelation. 111In-DTPA-IgG and DTPA-IgG were labelled with 14C through methylation. High-performance liquid chromatography (HPLC) and instant thin-layer chromatography analysis were performed to test the in vitro stability of the labelled proteins. Young Wistar rats with a Staphylococcus aureus infection of the left calf muscle were injected intravenously with 0.2 ml of a solution containing either 0.4 MBq 111In and 30 kBq 14C or 30 kBq 14C labelled to 80 micrograms IgG. Groups of five rats were sacrificed at 2, 6, 24, and 48 h. p.i. Activity uptake was determined for plasma, urine, abscess, muscle and various other tissues. Averages and standard deviations were calculated for groups of five rats. HPLC analysis was performed on plasma and urine samples taken up to 48 h p.i. The radiochemical purity of the IgG preparations was > 95%. The labelled preparations appeared stable in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of the route of administration on the biodistribution of radioiodinated OV-TL 3 F(ab')2 in experimental ovarian cancer.

The effect of the route administration on the distribution of radioiodinated OV-TL 3 F(ab')2 was studied in Balb/c female mice with intraperitoneal or subcutaneous ovarian carcinoma xenografts. In the intraperitoneal tumour model in which both ascites and solid tumour deposits were present, intraperitoneal administration resulted in a lower estimated radiation dose to blood as compared with intravenous administration. In this model normalization to equal estimated radiation doses to blood for both routes of administration indicated that a twice as high estimated radiation dose can be guided to solid intraperitoneal tumour deposits following intraperitoneal administration. Evacuation of ascitic tumour cells prior to monoclonal antibody injection further increased the estimated radiation dose to solid intraperitoneal tumour deposits following intraperitoneal delivery. Following simultaneous intravenous and intraperitoneal injection of the monoclonal antibody, tissue uptake showed no relevant differences in the subcutaneous tumour model. Overall, the intraperitoneal route of administration was found to be the best choice for therapeutic delivery of iodine-131 labelled monoclonal antibodies.

Is somatostatin receptor scintigraphy suited to detection of acute infectious disease?

Fast and accurate delineation of acute infectious foci is very important for adequate management of patients. All currently available scintigraphic techniques require a relatively long timespan between referral to the nuclear medicine department and final diagnosis. Small peptides that bind to receptors on cells in the infectious focus might improve the diagnostic possibilities. Since activated leukocytes express somatostatin receptors, 111In-octreotide, a somastostatin analogue, was tested for its usefulness in detecting acute infection in rats with a calf muscle infection caused by Staphylococcus aureus. 111In-octreotide was compared with the much larger protein 111In-labelled human nonspecific immunoglobulin G (111In-IgG). As early as 0.5 h after injection, the 111In-octreotide uptake in the abscess was significantly lower than that of 111In-IgG. Moreover, no 111In-octreotide retention in the abscess over time was noted. In conclusion, somatostatin receptor imaging does not allow scintigraphic detection of an acute infectious lesion. The uptake in an abscess is relatively poor compared to 111In-IgG.